Dry eye syndrome is generally known as keratoconjunctivitis sicca. Millions of people are suffering from this common eye disorders every year. There are many factors that can influence the risk of dry eye syndrome. The rapid development of electronic products is the most common reason for causing dry eye syndrome nowadays. With the rise in smart phones, tablet, laptop, etc. comes a strong increase in the number of dry eye disease patients. Therefore, to develop a treatment and prevention method for dry eye syndrome is an important research topic.
American Academy of Ophthalmology announced the definition of dry eye disease is that normal tear film has one of the following disorders: (1) decreased tear production or (2) excessive tear evaporation, an abnormality in the production of mucus or lipids normally found in the tear layer. Dry eye syndrome can also be divided into different levels base on the symptoms and severity. The symptoms of dry eye include dry, sleepy, itching, irritated eyes, excessively watery eyes, burning and stinging, a foreign body sensation, light sensation, and blurred vision. When the symptoms are severed, the patient's eye will be swollen, congestion and even cause vision damage, etc.
Substantiation risk factors of developing dry eye include aging, deficiency of male hormone secretion in postmenopausal women, lack of nutrients, alcoholism, corneal damage caused by infection or chemical burn, exophthalmoses of hyperthyroidism, facial or trigeminal nerve palsy, long-term contact lens wear and autoimmune diseases such as Sjögren's syndrome, systemic lupus erythematosus, erythemamultiforme and rheumatoid arthritis, etc.
Regular treatments for dry eye syndrome include artificial tears, surgical operation to remove punctual plugs and corticosteroid drops. In addition, the 0.05% cyclosporine is approved by FDA in 2003 to treat inflammation and androgen deficiency induced dry eye syndrome. Although these treatments can keep eyes moist, prevent tear evaporation and help with dryness of ocular surface, often used of these medications might increase not only the risk of the toxic and irritation effects but also give rise to drug resistant infections. As a consequence, non-steroidal anti-inflammatory drugs (NSAID) are increasingly used as dry eye treatment instead of steroids.
Nerve growth factor (NGF) was discovered in the 1950s, which is important for the growth, maintenance, and survival of certain target neurons (nerve cells). It also functions as a signaling molecule. There are two receptors Trk A and p75NTR. NGF and its receptors are also proven to be expressed by the rat lacrimal gland tissue, and also been quantified in human tears (Lee, H. K., et al., Am J Ophthalmol, 2005. 139(6): p. 965-71). Moreover, NGF has been shown to induce in vitro corneal epithelial cell proliferation and differentiation and in the tear film and corneal epithelium, which play an important role in ocular surface maintenance and corneal wound healing (Lambiase, A., et al., Invest Ophthalmol Vis Sci, 2009. 50(10): p. 4622-30). The NGF eye drops were found in the dog's dry eye model can increase tear secretion and conjunctival goblet cell density (Coassin, M., et al., Graefes Arch Clin Exp Ophthalmol, 2005. 243(2): p. 151-5). In clinical, the dry eye patients increased the NGF expression in tears, which is a compensatory mechanism of dry eye patients to maintain the normal function of the ocular surface (Lambiase, A., et al., Arch Ophthalmol, 2011. 129(8): p. 981-6). In addition, NGF can induce the conjunctival epithelial cells differentiate into goblet cell which has the ability to secrete mucin to protect the ocular surface (Lambiase, A., et al., Invest Ophthalmol Vis Sci, 2009. 50(10): p. 4622-30; and Lambiase, A., et al., Proc Natl Acad Sci USA, 2009. 106(32): p. 13469-74). However, these results show that regulation of NGF is a key factor of the treatment of dry eye and eye protection.
There remains a need for a safer and more effective treatment for dry eyes.